A variety of techniques have been used to bond or seal tissue. For example, different types of tissues have been mechanically bound or sealed with a number of procedures, materials and methods including sutures, staples, tapes and bandages. In some applications, these materials are made of absorbable materials which are intended to bond and/or seal tissue as it heals and then to be absorbed over a period of time.
The common use of a medical adhesive or "tissue glue" has not found widespread application. To date, some adhesive materials are known which may be used to adhere or stick tissue such as skin. For example, cyanoacrylate adhesives such as HISTOACRYL adhesive available from B. Braun, Melsungen, Germany or VETBOND tissue adhesive available from 3M, St. Paul, Minn. may be used to bond tissue. In addition to cyanoacrylate adhesives, other types of materials have been reported to adhere or stick to skin. For example, U.S. Pat. No. 4,839,345 to Doi et al. reports a hydrated crosslinked protein adhesive gel that is used as a cataplasm or cosmetic mask that will externally adhere to skin but can be easily removed or pulled off and then readhered to the skin. Other crosslinked protein hydrogels have been reported to serve as a proteinaceous substrate to deliver therapeutic agents such as enzymes or drugs through skin or mucous membranes. See, for example, International Patent Application Ser. No. PCT/US93/07314 filed Aug. 4, 1993. Still other materials have been used as hemostatic agents to stop or prevent bleeding. In particular, mixtures of fibrinogen and thrombin such as TISSEEL sealant available from Immuno AG, Vienna, Austria or BERIPLAST-P hemostatic agent or sealant available from Behringwerke, Marburg, Germany, have been used in vascular surgery to seal tissue such as blood vessels and thus prevent blood leakage.
In sum, there are few available adhesive compositions that have sufficient strength, biocompatibility and bioabsorbability as well as other desired properties that would allow such compositions to be readily used in current medical procedures or practices. The unavailability of a suitable tissue adhesive or sealant may be related to the stringent requirements that a suitable, useful tissue adhesive must meet. Importantly, a tissue adhesive must provide substantial bonding strength for either internal or external tissues. The adhesive should be made of a biocompatible material which does not interfere with normal healing or regeneration processes. A suitable tissue adhesive must also be easily administered in a liquid form and then rapidly cured, ideally in less than a minute, once applied. In addition, a tissue adhesive must remain flexible, pliant and have good mechanical strength after being cured. Finally, a tissue adhesive must be completely absorbed or broken down in vivo, without producing an allergic response, adverse tissue reaction or systemic toxic effects, in an acceptable time period. Preferably a suitable adhesive would also be readily absorbed after it is applied.